Accelerated starvation in late pregnancy: a comparison between obese women with and without gestational diabetes mellitus

We compared the glucose, insulin, free fatty acid, and 3-hydroxybutyrate responses to a briefly extended overnight fast during the third trimester of pregnancy between two groups: obese women with normal glucose tolerance (n = 10) and age- and weight-matched women with gestational diabetes mellitus (n = 10). After a 12-hour overnight fast, plasma glucose (95 +/- 4 vs. 78 +/- 2 mg/dl; p less than 0.01), insulin (32 +/- 5 vs. 17 +/- 2 microU/ml; p less than 0.02), and free fatty acid (860 +/- 63 vs. 639 +/- 79 mmol/L; p less than 0.05) levels were higher in the patients with gestational diabetes mellitus. 3-Hydroxybutyrate levels were similar in the two groups at that time (0.23 +/- 0.04 vs. 0.18 +/- 0.03 mmol/L; p greater than 0.3). When the fast was extended to 18 hours by having the patients skip breakfast, glucose levels fell more rapidly in the group with gestational diabetes mellitus but remained elevated compared with the nondiabetic women. Insulin levels declined at a similar rate in the two groups. Free fatty acid levels did not increase significantly in the group with gestational diabetes mellitus during the extended fast. In contrast, free fatty acid levels increased by 44% in the normal pregnant women, reaching the level observed in the group with gestational diabetes mellitus after 18 hours. 3-Hydroxybutyrate levels remained virtually identical in the two groups throughout the brief fast. Thus, compared with that of normal pregnant women, the response of obese women with gestational diabetes mellitus to brief caloric deprivation during late pregnancy was characterized by a greater fall in plasma glucose values without a greater propensity to ketosis. Our findings may have important implications for the dietary management of obese patients with gestational diabetes mellitus.     

Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes

We used the minimal model technique to obtain concurrent measurements of whole-body insulin sensitivity and pancreatic B-cell responsiveness to glucose during the third trimester of pregnancy. Insulin sensitivity in normal pregnant women (n = 8) was reduced to only one third that of a group of nonpregnant women (n = 7) of similar age and relative weight. This marked insulin resistance was compensated by reciprocal enhancement of the first and second-phase insulin responses to intravenous glucose, which were increased threefold as compared with the nonpregnant women. Women with gestational diabetes mellitus (n = 16) had mean insulin sensitivity that was similar to that of the normal pregnant group, which indicates that insulin action was appropriate for the late phase of pregnancy in the gestational diabetic group. By contrast, the mean first-phase insulin response was significantly reduced in women with gestational diabetes mellitus, as compared with that of normal pregnant women (p less than 0.001). However, approximately one fifth of the group with gestational diabetes mellitus had first-phase responses that did not fall below the 95% confidence interval for the mean in normal pregnant women. The mean second-phase response was also lower in the group with gestational diabetes, although the difference was of borderline statistical significance (p less than 0.09). Our findings reveal the quantitative nature of the reciprocal changes in insulin sensitivity and B-cell function that normally accompany late pregnancy. They further indicate that during the third trimester, mild gestational diabetes is characterized by an impairment of pancreatic B-cell function rather than an exaggeration of the normal insulin resistance of late pregnancy.     

Maternal plasma leptin levels and their relationship to insulin and glucose in gestational-onset diabetes

To investigate the changes in leptin levels and the relationship between this substance and insulin and glucose in pregnant women with gestational-onset diabetes, we measured plasma leptin levels in the maternal peripheral vein of 17 healthy and 17 diabetic women at 29 and 33 weeks of gestation. We also correlated maternal plasma leptin levels in diabetic women with fasting plasma insulin levels and plasma glucose levels obtained 1 h after oral administration of 50 g of glucose. Maternal serum leptin levels in women with gestational diabetes (mean +/- SD 16.52 +/- 5.07 ng/ml, range 10.84-27.4 ng/ml) were significantly higher (p < 0.001) than those found in uncomplicated pregnancies (10.61 +/- 1.47 ng/ml, range 7.28-13.4 ng/ml). A positive correlation was found between maternal serum leptin levels and glycosylated haemoglobin values in diabetic pregnant women (r = 0.94, p < 0.001). A positive correlation was also found between maternal leptin concentrations and fasting serum insulin levels, as well as between leptin concentrations and plasma glucose levels obtained 1 h after the administration of 50 g of glucose in women with gestational diabetes (r = 0.84, p < 0.001, and r = 0.92, p < 0.001, respectively). We conclude that leptin levels are elevated in pregnant women with gestational diabetes, and its metabolism depends on insulin levels and the severity of diabetes.     

Oral contraceptives and insulin receptor binding in normal women and those with previous gestational diabetes

The effect of a low-dose triphasic oral contraceptive (ethinyl estradiol and levonorgestrel) on glucose tolerance, plasma insulin response to a glucose challenge, and insulin receptor binding to monocytes and erythrocytes was investigated in seven women with previous gestational diabetes and seven nondiabetic control subjects. Investigations were performed in the luteal phase before the hormonal intake and after hormonal treatment for 2 and 6 months. Before treatment, women with previous gestational diabetes had significantly impaired glucose tolerance (p less than 0.05) when compared with the healthy controls, but no differences in insulin receptor binding were observed. Glucose tolerance and the insulin response to oral glucose remained unchanged in both groups during the treatment period. In the control subjects a significant decrease (p less than 0.05) in insulin receptor binding to monocytes was observed after hormonal intake for 6 months whereas the insulin receptor binding remained unchanged in the women with previous gestational diabetes. No correlation was found between the receptor binding data obtained from monocytes and erythrocytes in either group of women. The study demonstrates that in lean nondiabetic women and women with previous gestational diabetes of normal weight without first-degree history of diabetes there is no apparent direct association between glucose tolerance, plasma insulin levels, and insulin binding to erythrocytes and monocytes during intake of low-dose oral contraceptives.     

妊娠期糖尿病孕妇血清肿瘤坏死因子α水平变化与胰岛素抵抗关系的研究

目的　探讨妊娠期糖尿病孕妇血清肿瘤坏死因子α(TNF α)水平变化与胰岛素抵抗的关系。方法　采用酶联免疫吸附试验测定 4 2例妊娠期糖尿病孕妇 (GDM组 )、4 0例正常妊娠晚期孕妇 (正常妊娠组 )空腹血清TNF α水平 ;同时测定两组孕妇空腹血糖、C肽、胰岛素、糖化血红蛋白(HbA1c)水平。并且根据公式计算两组孕妇的胰岛素敏感指数 (ISI) ,以评价胰岛素抵抗程度。结果(1)GDM组孕妇空腹血清TNF α水平为 (5 2± 1 6 )ng/L ,正常妊娠组孕妇为 (4 5± 0 5 )ng/L ,两组比较 ,差异有极显著性 (P <0 0 1) ;GDM组孕妇ISI为 - 4 3± 0 4 ,正常妊娠组为 - 3 8± 0 3,两组比较 ,差异有极显著性 (P <0 0 1)。 (2 )GDM组孕妇空腹血糖、胰岛素、C肽水平分别为 (5 5± 0 7)mmol/L、(13 4± 3 8)mU/L、(1 6± 0 4 )nmol/L ,正常妊娠组孕妇空腹血糖、胰岛素、C肽水平分别为(4 9± 0 4 )mmol/L、(9 3± 2 5 )mU/L、(1 2± 0 3)nmol,两组比较 ,差异有极显著性 (P <0 0 1) ;GDM组孕妇HbA1c为 (5 6± 0 5 ) % ,正常妊娠组孕妇为 (5 3± 0 5 ) % ,两组比较 ,差异有显著性(P <0 0 5 )。 (3)GDM组孕妇空腹血清TNF α水平与ISI呈显著负相关 (r=- 0 70 3,P <0 0 1) ,分别与空腹血糖、C肽、HbA1c呈显著正相关 (r     

Does impaired glucose tolerance imply a risk in pregnancy?

Of 218 pregnant women with abnormal glucose tolerance by the criteria of the World Health Organization (1985) 81.2% had impaired glucose tolerance and 18.8% gestational diabetes. Gestational diabetic women were of higher parity, more obese, required insulin therapy more often, had more babies weighing greater than 4 kg and had higher fasting plasma glucose than women with impaired glucose tolerance. Women with gestational impaired glucose tolerance were older, of higher parity, more obese and had heavier babies than pregnant women with a normal screening plasma glucose. Compared with women with impaired glucose tolerance, gestational diabetic women were more likely to have abnormality, and more severe impairment of their glucose tolerance test in the puerperium.     

Demonstration of heterogeneity in gestational diabetes by a 400-kcal breakfast meal tolerance test

To evaluate the metabolic basis of gestational glucose intolerance (gestational diabetes), the response of normal pregnant women (N=6) and lean (N=23), and obese (N=12) gestational diabetics to the physiologic challenge of a 400-kcal mixed meal breakfast tolerance test was studied. Obese patients with gestational diabetes were more hyperglycemic than the lean gestational diabetics in both the fasting and postprandial periods. Women with gestational diabetes had a more prolonged glycemic response and a later insulin response to meal stimulation than normal control subjects. Fasting and postprandial insulin levels were higher in the obese gestational diabetes group, whereas those of lean subjects fell below the values of the control group. The percent specific binding of insulin to red blood cell receptors was lower in both gestational diabetes groups than in control subjects, with the most marked decrease in the obese group. Mean fasting plasma levels of total cholesterol and triglyceride and plasma glucagon levels during the meal tolerance test were not significantly different among the three groups. Obese gestational diabetics had significantly larger infants and placentas than lean gestational diabetics. These findings, taken together, suggest that the pathophysiology of gestational diabetes differs between obese and lean patients. Lean gestational diabetics appear to develop glucose intolerance on the basis of relative insulin deficiency in contrast to obese gestational diabetics who manifest glucose intolerance characterized by insulin resistance, hyperinsulinemia, and decreased insulin binding to red blood cell receptors.     

Does impaired glucose tolerance imply a risk in pregnancy?

Summary. Of 218 pregnant women with abnormal glucose tolerance by the criteria of the World Health Organization (1985) 81·2% had impaired glucose tolerance and 18·8% gestational diabetes. Gestational diabetic women were of higher parity, more obese, required insulin therapy more often, had more babies weighing >4 kg and had higher fasting plasma glucose than women with impaired glucose tolerance. Women with gestational impaired glucose tolerance were older, of higher parity, more obese and had heavier babies than pregnant women with a normal screening plasma glucose. Compared with women with impaired glucose tolerance, gestational diabetic women were more likely to have abnormality, and more severe impairment of their glucose tolerance test in the puerperium.     

Maternal serum adiponectin concentration in gestational diabetes

Aim. Adiponectin is an insulin sensitizing protein. Because gestational diabetes mellitus is associated with insulin resistance, we compared serum adiponectin levels in women with gestational diabetes mellitus and healthy pregnant women.

Study design. Twenty-nine women with gestational diabetes and 26 women with impaired glucose tolerance were compared with 27 normal pregnant women in control group. Controls were matched for gestational age, age and body mass index (BMI) before pregnancy with two other groups. At 28 weeks of gestation serum concentration of adiponectin, insulin and insulin resistance (calculated by the homeostasis model assessment) were measured in three groups.

Main findings. The serum adiponectin level in gestational diabetes (6379.31 ± 1934.90 ng/ml), was significantly lower than the impaired glucose tolerance test (7384.61 ± 1626.70 ng/ml) and control groups (7962.96 ± 2667.20 ng/ml),(p = 0.02). Serum level of insulin and HOMA index in gestational diabetes were higher than the normal group (p > 0.05). In patients with gestational diabetes, there was a significant correlation between serum adiponectin level and BMI before pregnancy (r = ?0.531, p = 0.013). Also, the correlation between maternal serum adiponectin levels and neonatal birth weight was not significant (r = ?0.07, p value = 0.73).

Conclusion. Our data show that serum adiponectin level was significantly lower in gestational diabetes in comparison with healthy pregnant women.     

Plasma insulin response following intravenous glucose in gestational diabetics

More insulin is needed to maintain glucose homeostasis during pregnancy. Pregnancy also has a diabetogenic effect on the mother, especially in genetically and obstetrically predisposed women. In the third trimester 195 pregnant women were screened for glucose tolerance by IVGTT (0.33 g/kg body-weight) and for plasma insulin response. In early puerperium the test was repeated. The results in gestational diabetics (k-value less than or equal to 1.0; n = 98) were to be compared to pregnant women with normal glucose tolerance (n = 97). Statistical methods (incl. discriminant analysis) were to verify differences in acute insulin release of the beta-cell and the cumulative insulin response following intravenous glucose. During the third trimester quantitatively more insulin is released when compared with early puerperium both in gestational diabetics and normal subjects (paired t-test p less than 0.01). A quantitative hypofunction of the beta-cells following intravenous glucose in gestational diabetics can be excluded. On the other hand, the most striking findings are a delayed insulin response in the initial phase of secretion (5-10 min) and significantly higher insulin levels during the late phase especially at the end of the test period (60 min) in gestational diabetics. In these cases a peripheral insulin resistance can be discussed. Hyperinsulinism is correlated to the clinical parameters overweight (greater than 10%) and the gaining of at least 12 kg of weight during pregnancy.     

Insulin-sensitivity index and carbohydrate and lipid metabolism in gestational diabetes

OBJECTIVE: To study insulin action in normal and gestational diabetic pregnant women by using an insulin tolerance test. STUDY DESIGN: Twenty-four women diagnosed as having gestational diabetes were compared to 22 nondiabetic, matched controls. The insulin-tolerance test (ITT) consisted of an intravenous bolus of 0.1 IU/kg of regular insulin with glucose sampling at -5, 0, 3, 5, 7, 10 and 15 minutes. The insulin sensitivity index (ISI) was assessed by using a delta G/G0 ratio (G0 = initial glycemia level, delta G = variation between G0 and glycemia level obtained at 15 minutes by calculation of the regression plot). RESULTS: Two women had glucose levels < 50 mg/dL at 15 minutes, without clinical symptoms. Women with gestational diabetes had a significantly lower level than those with normal glucose tolerance. The rate of abnormal insulin resistance (ISI) (< 10th percentile in the control group) was significantly higher in the insulin-treated subgroup (8/11, 72.7%, vs. 2/12, 16.6%). ISI correlated negatively with glycemia (r = -.38, P = .01) and glycosylated hemoglobin (r = -.50, P = .001) and correlated positively with low density lipoprotein-c (r = -.40, P = .01) and apolipoprotein B (r = -.42, P = .01). In the gestational diabetes group, ISI was correlated negatively with gestational age (r = -.50, P = .01) and triglycerides (r = -.50, P = .01). CONCLUSION: ITT seems to be a safe and rapid method of measuring in vivo insulin action in pregnant women. Women with gestational diabetes had higher insulin resistance, especially those who needed insulin therapy. Lipid profile in gestational diabetes was related to the level of insulin resistance.     

Prolactin and glucose tolerance in normal and gestational diabetic pregnancy

The relationship between the deterioration of glucose tolerance and plasma prolactin (PRL) levels was investigated in 15 normal pregnant women and in 15 women with gestational diabetes mellitus. Oral glucose tolerance tests were performed in late pregnancy and postpartum, and the insulin, glucagon, and PRL responses were measured. In late pregnancy the gestational diabetics revealed significantly elevated fasting glucose levels compared with the normal pregnant women and after the glucose challenge their insulin responses were significantly diminished and the suppression of glucagon less pronounced. These differences in glucose metabolism were markedly reduced early postpartum. There was no difference in basal PRL concentrations between the two groups neither in pregnancy nor postpartum. The PRL levels were not altered during the oral glucose tolerance tests and no correlation between the deterioration of glucose tolerance and the PRL concentrations could be demonstrated in either group. These results indicate that abnormal PRL levels are not of pathophysiologic importance for the development of gestational diabetes mellitus.     

Perinatal complications in women with gestational diabetes mellitus

BACKGROUND: The aim of the study was to examine the outcome of the pregnancy and neonatal period in 1) women with gestational diabetes mellitus and non-diabetic pregnant women, and 2) in women with early and late diagnosis of gestational diabetes mellitus. METHODS: Included were 327 women with gestational diabetes mellitus and 295 non-diabetic women, who were screened with a 75 g oral glucose tolerance test because of risk factors for gestational diabetes. Women with gestational diabetes mellitus were treated with low-caloric diet and insulin when appropriate, while women in the control group received routine antenatal care. RESULTS: Gestational age at delivery was significantly lower in the group with gestational diabetes mellitus, both when considering all deliveries (39.1+/-1.7 weeks versus 39.8+/-2.0 weeks, p<0.05) and only those with spontaneous onset of labor (38.8+/-2.0 weeks versus 40.0+/-1.6 weeks, p<0.05). The frequency of macrosomia was increased, although not statistically significant (8% vs. 2%, p=0.07), and the rate of admission to the neonatal ward was significantly increased (18% vs. 9%, p<0.05) in the group with gestational diabetes. Women with early diagnosis of gestational diabetes mellitus had a significantly increased need for insulin treatment during pregnancy (36% vs. 9% p<0.05) and a significantly higher occurrence of diabetes mellitus at follow-up from two months until three years postpartum. CONCLUSIONS: This study of women with gestational diabetes mellitus and non-diabetic pregnant women showed that gestational diabetes mellitus was associated with a significantly lower gestational age at delivery and an increased rate of admission to the neonatal ward. Women diagnosed with GDM before 20 weeks of gestation had an increased need for insulin treatment during pregnancy and a high risk of subsequent overt DM, compared with women diagnosed with GDM later in pregnancy.     

Vanadate enhances but does not normalize glucose transport and insulin receptor phosphorylation in skeletal muscle from obese women with gestational diabetes mellitus

OBJECTIVE: We compared the insulin-mimetic effects of vanadate, a protein-tyrosine phosphatase inhibitor, with the effects of insulin on skeletal muscle glucose transport and insulin receptor and insulin receptor substrate 1 phosphorylation to test the hypothesis that protein-tyrosine phosphatases participate in pregnancy-induced insulin resistance. STUDY DESIGN: Skeletal muscle fiber strips were obtained from the rectus abdominis during cesarean delivery in 7 patients with gestational diabetes mellitus, 11 pregnant women with normal glucose tolerance (pregnant control group), and 11 nonpregnant women undergoing elective surgery (nonpregnant control group). Muscle tissues were incubated in vitro for 15 to 60 minutes with or without maximal insulin (100 nmol/L) or sodium vanadate (6 micromol/L). Insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation were measured, as was 2-deoxyglucose transport. The levels of protein-tyrosine phosphatase 1B were measured by Western blot analysis. RESULTS: Vanadate stimulated maximal 2-deoxyglucose transport more than did insulin alone in all samples (P<.05), but the value was still less in muscle tissues from pregnant control subjects and patients with gestational diabetes mellitus (P<.05). In muscle tissues from pregnant control subjects vanadate increased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 to levels similar to those in muscle tissues from nonpregnant control subjects. In patients with gestational diabetes mellitus vanadate increased insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation, but these values remained less than in muscle tissues from nonpregnant control subjects (P<.05). Protein-tyrosine phosphatase 1B levels were not significantly different in skeletal muscles from each group. CONCLUSION: Vanadate did not restore normal glucose transport activity during pregnancy complicated by gestational diabetes mellitus, which indicates that decreased glucose uptake is probably not caused by impaired tyrosine phosphorylation events alone. Increased serine kinase activity and impaired glucose transporter 4 translocation probably contribute to insulin signaling abnormalities associated with pregnancy, especially in patients with gestational diabetes mellitus.     

妊娠期糖尿病孕妇外周血、脐血及胎盘中的chemerin表达

目的:探讨正常孕妇和妊娠期糖尿病(GDM)患者外周血、脐血以及胎盘中趋化素(chemerin)的表达差异及其临床意义。方法:选取2010年10月至2011年10月上海交通大学医学院附属第一人民医院20例正常孕妇及20例GDM孕妇。应用ELISA法检测外周血及脐血中chemerin水平,Western blot法测定其在胎盘中的表达,并分析其与临床相关特征的关系。结果:chemerin在正常孕妇和GDM孕妇外周血中的表达无显著差异,而在脐血和胎盘中的表达差异显著(P<0.05),与空腹血糖、餐后2h血糖、空腹胰岛素、胰岛素抵抗指数(HOMA-IR)、C反应蛋白(CRP)、胰岛素用量呈正相关(P<0.05)。结论:chemerin是影响GDM的一个独立因素,在GDM孕妇的脐血和胎盘中表达较高,并随着胰岛素用量的增加而表达增多,其可能通过糖代谢途径及炎症反应在GDM的发生发展中起着重要作用。     

Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus.

OBJECTIVES: The purpose of this study was to determine the incidence of diabetes in women with previous dietary-treated gestational diabetes mellitus and to identify predictive factors for development of diabetes. STUDY DESIGN: Two to 11 years post partum, glucose tolerance was investigated in 241 women with previous dietary-treated gestational diabetes mellitus and 57 women without previous gestational diabetes mellitus (control group). RESULTS: Diabetes developed in 42 (17.4%) women with previous gestational diabetes mellitus (3.7% insulin-dependent diabetes mellitus and 13.7% non-insulin-dependent diabetes mellitus). Diabetes did not develop in any of the controls. Predictive factors for diabetes development were fasting glucose level at diagnosis (high glucose, high risk), preterm delivery, and an oral glucose tolerance test result that showed diabetes 2 months post partum. In a subgroup of previous patients with gestational diabetes mellitus in whom plasma insulin was measured during an oral glucose tolerance test in late pregnancy a low insulin response at diagnosis was found to be an independent predictive factor for diabetes development. CONCLUSIONS: Women with previous dietary-treated gestational diabetes mellitus have a considerably increased risk of later having diabetes. Follow-up investigations are therefore important, especially in those women with previous gestational diabetes mellitus in whom the identified predictive factors are present.     

When is fasting really fasting? The influence of time of day, interval after a meal, and maternal body mass on maternal glycemia in gestational diabetes.

OBJECTIVE: The object of the study was to determine whether time of day, interval after a standard meal, and maternal body mass influence plasma glucose concentrations in women with gestational diabetes mellitus. STUDY DESIGN: Identical mixed meals were administered on 2 separate occasions 1 week apart to 30 women with dietarily treated gestational diabetes and pregnancies between 28 and 38 weeks' gestation. One meal was administered at 7 AM (morning meal) and the other was administered at 9 PM (evening meal), each after a fast of >/=5 hours. The order of the meals (morning first versus evening first) was assigned randomly. Sixteen of the women had a body mass index >/=27 kg/m(2) (overweight) and 14 women had a body mass index <27 kg/m(2) (lean). Venous plasma concentrations of glucose, insulin, free fatty acids, beta-hydroxybutyrate, and bound and free cortisol were measured hourly for 9 hours after each of the test meals. RESULTS: When all women were considered together glucose concentrations after the morning meal were significantly greater at 1 hour, were not different at 2 hours, and were significantly lower from 3 through 9 hours postprandially than those at corresponding times after the evening meal. Plasma beta-hydroxybutyrate and free fatty acid concentrations were higher between 5 and 9 hours after the morning meal than at the same times after the evening meal. Total and free cortisol levels were higher for the first 7 hours after the morning feeding, reflecting known diurnal variation in cortisol concentrations. Overweight patients' glucose values were significantly greater than those of lean subjects during the last 4 hours of the overnight fast. CONCLUSIONS: Among women with dietarily treated gestational diabetes the glucose concentrations were significantly higher from 3 to 9 hours after an evening meal, whereas suppression of free fatty acids and beta-hydroxybutyrate was less sustained after a morning feeding. The mechanisms underlying these differences remain to be determined but may involve diurnal influences of counterregulatory hormones. The relationships between measurements of maternal glycemia and maternal and perinatal outcomes in pregnancies complicated by gestational diabetes may be clarified by establishing a uniform duration of a fast and by developing meal-specific preprandial and postprandial maternal glucose targets for these patients.     

Normal secretion of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 during gestational diabetes mellitus.

BACKGROUND AND AIM: Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2) are suggested to be caused by the same metabolic disorder. Defects in gut hormone-dependent regulation of beta-cell function (entero-insular axis) have been proposed to contribute to the pathogenesis of DM2. The aim of study was to evaluate whether an impaired secretion of glucagon-like peptide-1 (GLP-1) and/or glucose-dependent insulinotropic polypeptide (GIP) could play a role in the development of carbohydrate disorders during pregnancy. SUBJECTS AND METHODS: The study group (GDM) consisted of 13 gestational women with diabetes mellitus in whom GDM was diagnosed according to the World Health Organization criteria (75-g oral glucose tolerance test (OGTT)). The control group consisted of 13 pregnant women with normal glucose tolerance (NGT), matched according to age and duration of pregnancy. For all patients, plasma glucose, insulin, GLP-1 and GIP concentrations were evaluated after an OGTT, i.e. at 0, 30, 60, 90 and 120 min after glucose load. RESULTS: Fasting plasma glucose concentrations were similar in both groups, but the 0-120 min area under the curve (AUC) for glucose was significantly greater in the GDM group than in the NGT group (p < 0.0005). Fasting insulin concentration was higher (p < 0.05) and the 2-h insulin response (AUCtotal) was significantly greater (p = 0.01) in the GDM group than in the NGT group. Insulin resistance was significantly higher in GDM compared with control women (homeostasis model assessment, p = 0.003). Fasting GLP-1 concentrations were higher in the GDM group (p = 0.05), but no differences were observed in GLP-1 response (AUC) between the studied groups. Fasting and stimulated GIP response did not differ between groups at any time of the study (p > 0.05). Positive correlations were observed between fasting GLP-1 and insulin concentration (r = 0.56, p < 0.004) and between fasting GLP-1 and insulin resistance (r = 0.43, p < 0.029). CONCLUSION: An impaired secretion of GLP-1 and GIP does not seem to play a major role in the pathogenesis of GDM.     

妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖关系的研究

目的　探讨妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖的关系。方法　采用放射免疫法 ,测定 36例妊娠期糖代谢异常孕妇 (糖代谢异常组 )和 2 4例正常孕妇 (正常妊娠组 )的空腹及口服 50g葡萄糖后 3h的血清瘦素水平 ;采用电化学发光法测定两组孕妇的空腹血清胰岛素水平 ;采用低压液相色谱分析法测定两组孕妇的糖化血红蛋白 ;采用葡萄糖氧化酶法测定两组孕妇的口服 50g葡萄糖后 1h的血糖水平。结果　 (1 )糖代谢异常组孕妇血清瘦素水平为 (1 4 9± 4 3) μg/L ,正常妊娠组为 (1 0 0± 1 8) μg/L ,两组比较 ,差异有极显著性 (P <0 0 1 ) ;(2 )糖代谢异常组孕妇空腹血清胰岛素、糖化血红蛋白、服糖后 1h血糖水平分别为 (1 2 9± 4 3)mU/L、 (6 1± 1 1 ) %、(1 1 0±1 4)mmol/L ;正常妊娠组孕妇分别为 (8 6± 3 2 )mU/L、(4 5± 1 0 ) %、(7 8± 1 2 )mmol/L。糖代谢异常组孕妇血清瘦素水平与空腹血清胰岛素、糖化血红蛋白、服糖后 1h的血糖水平呈明显的正相关关系 ,相关系数 (r)分别为 0 835、0 758、0 561。结论　妊娠期糖代谢异常孕妇空腹血清瘦素水平升高 ,其瘦素水平的高低与空腹血清胰岛素及血糖水平相关     

Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus

OBJECTIVE: This study prospectively evaluated the longitudinal changes in insulin sensitivity, insulin response, and endogenous (primarily hepatic) glucose production and suppression during insulin infusion in women with normal glucose tolerance (control) and gestational diabetes mellitus before and during a planned pregnancy. STUDY DESIGN: Eight control subjects and 7 subjects in whom gestational diabetes mellitus developed were evaluated with an oral glucose tolerance test, an intravenous glucose tolerance test, and hyperinsulinemic-euglycemic clamp with infusion of [6,6 (2)H2 ]glucose before conception and at 12 to 14 and 34 to 36 weeks' gestation. Insulin response was estimated as the area under the curve during the intravenous glucose tolerance test. Basal endogenous glucose production was estimated from isotope tracer dilution during steady state with [6,6 (2)H2 ]glucose and suppression during insulin infusion. Insulin sensitivity to glucose was defined as the glucose infusion rate required to maintain euglycemia during steady-state insulin infusion. Body composition was estimated with hydrodensitometry. Data were analyzed with 2-way analysis of variance with repeated measures for 2 groups. RESULTS: There were increases in first-phase (P =.006) and second-phase (P =. 0001) insulin responses in both groups with advancing gestation, but the increase in second-phase response was significantly greater (P =. 02) in the gestational diabetes mellitus group than in the control group. Basal glucose production increased significantly (P =.0001) with advancing gestation, and there was resistance to suppression during insulin infusion in both groups (P =.0001). There was less suppression of endogenous glucose production however, in the gestational diabetes mellitus group than in the control group (P =. 01). Insulin sensitivity decreased with advancing gestation in both groups (P =.0001), and there was lower insulin sensitivity in the gestational diabetes mellitus group than in the control group (P =. 04). Significant decreases in insulin sensitivity with time (P =. 0001) and between groups (P =.03) remained when the data were adjusted for differences in insulin concentration or residual hepatic glucose production. CONCLUSION: Obese women in whom gestational diabetes mellitus develops have a significant increase in insulin response but decreases in insulin sensitivity and suppression of hepatic glucose production during insulin infusion with advancing gestation with respect to a matched control group. These metabolic abnormalities in glucose metabolism are the hallmarks of type 2 diabetes, for which these women are at increased risk in later life.